T-cell antigen recognition requires antigen presenting cells (APCs) to present antigen fragments (peptides) on their cell surface in association with molecules of the major histocompatibility complex (MHC). T cells use their antigen specific T-cell receptors (TCRs) to recognise the antigen fragments presented by the APC. Such recognition acts as a trigger to the immune system to generate a range of responses to eradicate the antigen which has been recognised.
Recognition of external antigens by the immune system of an organism, such as man, can in some cases result in diseases, known as atopic conditions. Examples of the latter are the allergic diseases including asthma, atopic dermatitis and allergic rhinitis. In this group of diseases, B lymphocytes generate antibodies of the IgE class (in humans) which bind externally derived antigens, which are referred to in this context as allergens since these molecules elicit an allergic response. Production of allergen-specific IgE is dependent upon T lymphocytes which are also activated by (are specific for) the allergen. Allergen-specific IgE antibodies bind to the surface of cells such as basophils and mast cells by virtue of the expression by these cells of surface receptors for IgE.
Crosslinking of surface bound IgE molecules by allergen results in degranulation of these effector cells causing release of inflammatory mediators such as histamine, 5-hydroxtryptamine and lipid mediators such as the sulphidoleukotrienes. In addition to IgE-dependent events, certain allergic diseases such as asthma are characterised by IgE-independent events.
Allergic IgE-mediated diseases are currently treated with agents which provide symptomatic relief or prevention. Examples of such agents are anti-histamines, β2 agonists, and glucocorticosteroids. In addition, some IgE-mediated diseases are treated by desensitisation procedures that involve the periodic injection of allergen components or extracts. Desensitisation treatments may induce an IgG response that competes with IgE for allergen, or they may induce specific suppressor T cells that block the synthesis of IgE directed against allergen. This form of treatment is not always effective and poses the risk of provoking serious side effects, particularly general anaphylactic shock. This can be fatal unless recognised immediately and treated with adrenaline. A therapeutic treatment that would decrease or eliminate the unwanted allergic-immune response to a particular allergen, without altering the immune reactivity to other foreign antigens or triggering an allergic response itself would be of great benefit to allergic individuals.
Pollen allergens are recognised as a major cause of allergic diseases in humans and animals, including asthma, allergic rhinitis and allergic dermatitis. At least 10% of the population of the USA suffers from pollen allergies at various times and to varying extents. Proteins present in tree pollen, in particular from trees of the order Fagales, for example birch, alder, hazel, hornbeam and oak, are particularly important. Of these species, birch pollen allergens are the most frequent initiators of allergic responses to tree pollen (Jarolim et al: Allergy 1989; 44(6):385-95). For example, approximately 25% of hayfever sufferers are responsive to birch pollen. Hayfever is the common term for a form of seasonal allergy characterised by sneezing, runny nose and itching eyes. Allergy to tree pollen is most problematic during the spring months, with the birch pollen season typically occurring around April (in the northern hemisphere). However, some related types of tree such as alder and hazel can release airborne pollen as early as January (northern hemisphere). These are followed by elm, willow and ash in March, with oak in late April and early May.
It has been calculated that for adults in the United States, hayfever is the 5th leading chronic disease and a major cause of work absenteeism, resulting in nearly 4 million missed or lost workdays each year, resulting in a total cost of more than $700 million in total lost productivity. Allergies are also the most frequently reported chronic condition in children, limiting activities for more than 40% of them. Each year, allergies account for more than 17 million outpatient office visits in the United States; seasonal allergies such as hayfever account for more than half of these allergy visits.
A therapeutic or preventative treatment would therefore be of great benefit to humans that suffer or are at risk of suffering from tree allergy.